{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:40:49Z","timestamp":1777506049245,"version":"3.51.4"},"reference-count":22,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2015,11,5]],"date-time":"2015-11-05T00:00:00Z","timestamp":1446681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council of Australia"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81228013"],"award-info":[{"award-number":["81228013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Arthritis foundation of Australia, The University of Western Australia (UWA) Research Collaboration Awards"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteolytic bone diseases are commonly presented with enhanced osteoclast formation and bone resorption. Sesquiterpene lactone natural compounds have been found to possess  anti-inflammatory and immune-modulation effects. Here, we identified three germacrane sesquiterpenes using computer-based virtual screening for the structural similarity with sesquiterpene lactone, parthenolide. We showed that natural germacrane sesquiterpene compounds A, B, and C inhibit osteoclast formation and bone resorption in a dose-dependent manner, with relative potency compound A &gt; compound C &gt; compound B based on their equimolar concentrations. Mechanistic studies by Luciferase reporter gene assay and Western blot analysis showed that germacrane sesquiterpene compound A inhibits RANKL-induced activation of NF-\u03baB and I\u03baB\u03b1 degradation. This study reveals that natural germacrane sesquiterpene compounds are inhibitors for osteoclast formation and bone resorption, and provides evidence that naturally-occurring compounds might be beneficial as alternative medicine for the prevention and treatment of osteolysis.<\/jats:p>","DOI":"10.3390\/ijms161125972","type":"journal-article","created":{"date-parts":[[2015,11,5]],"date-time":"2015-11-05T10:56:04Z","timestamp":1446720964000},"page":"26599-26607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Natural Germacrane Sesquiterpenes Inhibit Osteoclast Formation, Bone Resorption,  RANKL-Induced NF-\u03baB Activation, and  I\u03baB\u03b1 Degradation"],"prefix":"10.3390","volume":"16","author":[{"given":"Shengnan","family":"Qin","sequence":"first","affiliation":[{"name":"Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estabelle","family":"Ang","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libing","family":"Dai","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongping","family":"Ye","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China"},{"name":"School of Pathology and Laboratory Medicine, the University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honghui","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pathology and Laboratory Medicine, the University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingli","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pathology and Laboratory Medicine, the University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dian","family":"Teguh","sequence":"additional","affiliation":[{"name":"School of Pathology and Laboratory Medicine, the University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renxiang","family":"Tan","sequence":"additional","affiliation":[{"name":"Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Xu","sequence":"additional","affiliation":[{"name":"Research Center for Drug Discovery (RCDD), School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Circle at University City, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Tickner","sequence":"additional","affiliation":[{"name":"School of Pathology and Laboratory Medicine, the University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Pavlos","sequence":"additional","affiliation":[{"name":"Centre for Orthopaedic Research, School of Surgery, the University of Western Australia,  Perth, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiake","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China"},{"name":"School of Pathology and Laboratory Medicine, the University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","article-title":"Bone resorption by 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